Pirfenidone Induced Photosensitivity Reaction in a Patient with Idiopathic Pulmonary Fibrosis

Drug-induced photosensitivity refers to the development of cutaneous disease as a result of combined effects of a chemical and light. Photosensitivity reactions may result from systemic medications and topically applied compounds. Pirfenidone is known to cause photosensitivity reactions, rash, pruritus and dry skin at high doses. However, similar adverse reactions with low doses of Pirfenidone have not been reported. We report a case of photosensitivity reaction induced by low- dose Pirfenidone in a patient with idiopathic pulmonary fibrosis (IPF)

MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors

BACKGROUND MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated. METHODS Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets. RESULTS Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change. CONCLUSIONS Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers

Phosphorylated ERK is a potential predictor of sensitivity to sorafenib when treating hepatocellular carcinoma: evidence from an in vitro study

<p>Abstract</p> <p>Background</p> <p>Sorafenib is the first agent that has demonstrated an improved overall survival benefit in advanced hepatocellular carcinoma (HCC), setting a new standard for first-line treatment. However, no one has yet been able to predict sensitivity to sorafenib. Pre-treatment pERK level has been shown to be associated with favorable response to such therapy in a phase II clinical study, indicating that pERK may be a potential biomarker for treatment of HCC with sorafenib.</p> <p>Methods</p> <p>The effects of sorafenib and 5-fluorouracil (5-FU) on cell proliferation were evaluated by cell viability assays in four HCC cell lines (SMMC-7721, MHCC97-L, MHCC97-H and HCCLM6) with different metastatic potential and basal pERK expression levels. Expression levels of pERK were determined by immunocytochemical quantification together with western blot analysis, and pERK density values were also calculated. Correlation analyses were then carried out between the IC₅₀values of drugs and pERK density values. After basal ERK phosphorylation was down-regulated with U0126 in MHCC97-H cells, cellular responsiveness to sorafenib was assessed by cell viability assay.</p> <p>Results</p> <p>Basal pERK levels increased stepwise in cell lines in accordance with their metastatic potential. Sorafenib inhibited ERK phosphorylation in a dose-dependent manner in all four cell lines at a concentration between 5 and 20 μM, but the degree of inhibition was significantly different according to their basal pERK expression level (<it>P </it>< 0.0001). In contrast, no significant change was observed after 5-FU treatment. Correlation analyses between the IC₅₀values and pERK densities revealed that the effects of sorafenib on cell proliferation were significantly correlated with basal pERK levels (Spearman r = -0.8671, <it>P </it>= 0.0003). Resistance to 5-FU was also significantly associated with basal pERK expression in these HCC cell lines (Spearman r = 0.7832, <it>P </it>= 0.0026). After the basal ERK phosphorylation level in MHCC97-H cells was reduced with U0126, they were significantly less sensitive to sorafenib-mediated growth inhibition, with an IC₅₀of 17.31 ± 1.62 μM versus 10.81 ± 1.24 μM (<it>P </it>= 0.0281).</p> <p>Conclusion</p> <p>In this <it>in vitro </it>study, pERK was confirmed to be a potential biomarker predictive of sensitivity to sorafenib in treating HCC. The RAF/MEK/ERK pathway may be involved in drug resistance to traditional chemotherapy in HCC.</p

Nutritional Indices of the Cotton Bollworm, Helicoverpa armigera, on 13 Soybean Varieties

The effects of 13 soybean varieties (356, M4, M7, M9, Clark, Sahar, JK, BP, Williams, L17, Zane, Gorgan3, and DPX) on nutritional indices of the cotton bollworm, Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae), were determined at 25 ± 1° C, 65 ± 5% RH and a photoperiod of 16:8 L:D. Fourth instar larvae reared on Zane showed the highest efficiency of conversion of digested food (ECD) and approximate digestibility (AD) values (0.299 and 0.867, respectively) compared with other varieties. The lowest value of ECD and food consumed (FC) was on 356 (0.133 and 53.82 mg, respectively). The highest and lowest efficiency of conversion of ingested food (ECI) of fifth instar larvae (0.235 and 0.156, respectively) were on Zane and M4, respectively. The ECI and ECD values of whole larval instars were the highest on M7 (0.524 and 0.820, respectively) and lowest on Sahar (0.279 and 0.353, respectively). However, the highest and lowest value of consumption index (CI) was on M7 (7.351) and BP (3.462). Among the different varieties of soybean, the highest AD value was on M9 (0.858), and the lowest was on Zane (0.597). The results indicated that M4, Sahar, and JK were partially resistant to H. armigera

Recurrence of Diabetic Pedal Ulcerations Following Tendo-Achilles Lengthening

Foot and ankle surgeons are frequently challenged by the devastating systemic consequences of diabetes mellitus manifested through neuropathy, integumentary and joint breakdown, delayed healing, decreased ability to fight infection, and fragile tendon/ligaments. Diabetic neuropathic pedal ulcerations lead to amputations at an alarming rate and also carry a high mortality rate. This article will discuss causes of diabetic pedal ulcerations that persist or recur after tendo-Achilles lengthening and will highlight areas that need to be addressed by the practitioner such as infection, vascular and nutritional status, glucose control, off-loading, biomechanics, and patient compliance

Burden and predictors of hypertension in India: results of SEEK (Screening and Early Evaluation of Kidney Disease) study

Background: Hypertension (HTN) is one of the major causes of cardiovascular morbidity and mortality. The objective of the study was to investigate the burden and predictors of HTN in India. Methods: 6120 subjects participated in the Screening and Early Evaluation of Kidney disease (SEEK), a community-based screening program in 53 camps in 13 representative geographic locations in India. Of these, 5929 had recorded blood pressure (BP) measurements. Potential predictors of HTN were collected using a structured questionnaire for SEEK study. Results: HTN was observed in 43.5% of our cohort. After adjusting for center variation (p < 0.0001), predictors of a higher prevalence of HTN were older age ≥40 years (p < 0.0001), BMI of ≥ 23 Kg/M2 (p < 0.0004), larger waist circumference (p < 0.0001), working in sedentary occupation (p < 0.0001), having diabetes mellitus (p < 0.0001), having proteinuria (p < 0.0016), and increased serum creatinine (p < 0.0001). High school/some college education (p = 0.0016), versus less than 9th grade education, was related with lower prevalence of HTN. Of note, proteinuria and CKD were observed in 19% and 23.5% of HTN subjects. About half (54%) of the hypertensive subjects were aware of their hypertension status. Conclusions: HTN was common in this cohort from India. Older age, BMI ≥ 23 Kg/M2, waist circumference, sedentary occupation, education less, diabetes mellitus, presence of proteinuria, and raised serum creatinine were significant predictors of hypertension. Our data suggest that HTN is a major public health problem in India with low awareness, and requires aggressive community-based screening and education to improve health

In utero exposure to butyl benzyl phthalate induces modifications in the morphology and the gene expression profile of the mammary gland: an experimental study in rats

<p>Abstract</p> <p>Background</p> <p>Environmental estrogens are exogenous estrogen-mimicking compounds that can interfere with endogenous endocrine systems. Several of these endocrine disruptors have been shown to alter normal development and influence tumorigenesis in experimental models. N-butyl benzyl phthalate (BBP), a widely used plasticizer, is a well-known endocrine disruptor. The aim of this study was to elucidate the effect of prenatal exposure to BBP on the morphology, proliferative index, and genomic signature of the rat mammary gland at different ages.</p> <p>Methods</p> <p><it>In utero </it>exposure was performed by gavage of pregnant Sprague Dawley CD rats with 120mg or 500mg BBP/kg/day from day 10 post-conception to delivery. Female litters were euthanized at 21, 35, 50 and 100 days. The morphology and proliferative index of the mammary gland were studied from whole mount preparations and BrdU incorporation, respectively. Gene expression profile was assessed by microarrays. Several genes found differentially expressed and related to different functional categories were further validated by real time RT-PCR.</p> <p>Results</p> <p>Prenatal exposure of BBP induced delayed vaginal opening and changes in the post-natal mammary gland long after the end of the treatment, mainly by 35 days of age. Exposure to the high dose resulted in modifications in architecture and proliferative index of the mammary gland, mostly affecting the undifferentiated terminal end buds. Moreover, the expression profiles of this gland in the exposed rats were modified in a dose-dependent fashion. Analysis of functional categories showed that modified genes were related to immune function, cell signaling, proliferation and differentiation, or metabolism.</p> <p>Conclusions</p> <p>Our data suggest that <it>in utero </it>exposure to BBP induced a delayed pubertal onset and modified morphology of the mammary gland. These alterations were accompanied by modifications in gene expression previously associated with an increased susceptibility to carcinogenesis.</p